Sequential first-line therapy in metastatic colorectal cancer with Capecitabine/FUFA, Irinotecan and Bevacizumab
- Conditions
- metastatic colorectal cancerMedDRA version: 20.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2009-013099-38-DE
- Lead Sponsor
- Klinikum der Universität München, Anstalt des öffentlichen Rechts vertreten durch den Vorstand
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 450
Female and male patients can be included in the trial when all following inclusion criteria are met:
- patient's informed consent in written form
- histologically confirmed metastatic colorectal cancer
- metastases are not resectable or the patient can not or does not wish to undergo surgical treatment
- no prior chemotherapy of the metastatic disease
- measurable metastases according to RECIST version 1.1 (CT Thorax/Abdomen within 4 weeks before registration)
- age = 18 years
- ECOG performance status 0-1
- Life expectancy > 3 months
- Evaluation of the KRAS status (decentralized conduction, result is no requirement at time of inclusion)
- patient agrees to asservation of tumor material for the purpose of molecular analyses including determination of the genetic profile of the tumor
- time interval to prior adjuvant chemotherapies > 6 months
- time interval to prior major surgical interventions, open biopsies or significant traumatic damages = 28 days, to port implantations or minor surgical interventions = 7 days, for placement of CVL = 2 days
- women of child bearing potential have to apply adequate contraceptive methods
- exclusion of an existing pregnancy
- normal cardiac function (LVEF = 55%) confirmed by ECG and echocardiography
- patients who do not receive anticoagulation, have to have an INR value < 1.5 ULN and PTT < 1.5 ULN. The application of a therapeutically dosed anticoagulation is allowed, as long as INR- and PTT values are within the therapeutic range and the patient is at least 2 weeks under stable dosage of the anticoagulant.
- A continuous medication with ASS up to a dose of 325 mg/day ist allowed. Furthermore, administration of Clopidogrel up to a recommended dose of 75 mg/day or of Ticlopidin up to a recommended dose of 2 x 250 mg/day is allowed. However, a combination of ASS with Clopidogrel or with Ticlopidin is not allowed.
- Patients with < 2 + proteinuria in the urine dipstick analysis. A 24 hr urine collection analysis should be done for patients with 2 + proteinuria in the urine dipstick analysis at baseline and proteinuria should be = 1 g per 24 hrs
- Patients suffered from thrombosis grade 3-4 (NCI CTCAE Version 4.0) in their medical history must recieve prophylactic anticoagulation
- appropriate organ function as defined below:
Hematological
Neutrophiles = 1.5000/µL
Hemoglobin = 9 g/dL
Platelets = 100.000/µL
Hepatic
Albumin = 2.5 g/dL
Serum Bilirubin = 1.5 ULN
AST and ALT = 2.5 x ULN
= 5.0 x ULN with hepatic metastasis
Renal
Serum creatinine = 1.5 mg/dL
or cacluated Creatinine clearance = 50 mL/min (GFR: Cockroft-Gault)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of
A patient can not be included in the trial, if one of the following criteria is met:
- Primarily resectable metastases and patient’s wish to undergo surgical intervention
- Heart insufficiency grade III or IV (functional NYHA classification)
- Existing concomitant disease or condition, which classifies the patient unsuitable for the trial or would interfere with the patient’s safety
- Myocardial infarction, instable angina pectoris, cardiac angioplasty or stent placement within the last 6 months
- History of an arterial thromboembolism including stroke, transient ischemic attack or cerebrovascular disease within the last 6 months
- Severe bleeding within the last 6 months (excluding tumor bleeding before resection), coagulopathy or bleeding diathesis
- Abdominal or tracheo-oesophageal fistulas, gastrointestinal perforations within the last 6 months prior to enrolment into the study
- not adequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and /or >100 mmHg diastolic blood pressure) under antihypertensive therapy
- History of recurring thromboembolic events (> 1 episode of deep vein thrombosis, peripherally embolism) during the last 2 years
- Severe wound healing impairment or ulcerations or bone fractures
- Pregnant or lactating patients
- any psychological, family related, sociological or geographic occurrence, which does not allow compliance to the study protocol
- Additional cancer therapy (chemotherapy, radiation, biological therapy, immunotherapy or hormonal therapy) during the course of the trial
- Concomitant treatment with other trial medication, any other explicitly prohibited medication during the course of the trial or participation in another clinical trial
- Contraindications for treatment with irinotecan and/or FUFA
- Any known immediate or delayed hypersensitivity reaction or idiosyncrasy to pharmaceuticals chemically related to Capecitabine, 5-fluorouracil, folinic acid, Irinotecan or Bevacizumab
- Acute or subacute ileus or chronic inflammatory bowel disease
- Known glucuronidation defect (Gilbert-Meulengracht-Syndrome)
- Untreated brain metastases
- Known secondary malignant neoplasm within the last 5 years (excluding basal cell carcinoma or in situ carcinoma of the cervix)
- known alcohol or drug abuse
- missing or limited legal capacity
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method